The causal effects of body mass index (BMI) on childhood symptoms of depression, anxiety disorder, and attention-deficit hyperactivity disorder: a within family Mendelian randomization study

ObjectivesHigher BMI in childhood predicts neurodevelopmental and emotional problems, but it is unclear if these associations are causal. Previous genetic studies imply causal effects of childhood BMI on depression and attention-deficit hyperactivity disorder (ADHD), but these observations might also reflect effects of demography and the family environment. We used within-family Mendelian randomization, which accounts for familial effects by controlling for parental genotype, to investigate the impact of BMI on symptoms of depression, anxiety, and ADHD symptoms at age 8. MethodsThis study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). Participants were 26,370 8-year-old children (48.7% female) born 1999-2009, together with their parents. We applied multivariable regression, classic Mendelian randomization ( classic MR), and within-family Mendelian randomization ( within-family MR). We report estimates of the effects of the childs own BMI, mothers BMI, and fathers BMI on the childs depressive, anxiety, and ADHD symptoms, reported by mothers when the child was aged 8. ResultsIn multivariable regression, higher BMI was marginally associated with more depressive and ADHD symptoms, and associated with fewer anxiety symptoms, in 8-year-old children. Classic MR models implied a causal effect of childrens higher BMI on higher depressive and ADHD symptoms, and to a lesser degree, lower anxiety symptoms. In within-family MR models, there was less evidence that childrens own BMI affected any of these symptoms. For example, a 5kg/m2 increase in BMI was associated with 0.04 standard deviations (SD) higher depressive symptoms (95% CI -0.01 to 0.09) in multivariable regression, with corresponding effect estimates of 0.41 SD (95% CI 0.10 to 0.56) in classic MR and 0.08 SD (95% CI -0.25 to 0.42) in within-family MR. Within-family MR suggested that maternal but not paternal BMI was associated with childrens depressive symptoms. ConclusionsThe influence of childhood BMI on depressive, anxiety and ADHD symptoms may have been overstated by MR approaches that do not account for parental genotype. Factors correlated with maternal BMI may influence offspring symptoms of depression. What is already known on this topicO_LIChildren with high body mass index have been found to have more symptoms of depression, anxiety, and attention-deficit hyperactivity disorder. C_LIO_LIIt is not known whether higher body weight increases risk of these symptoms, these symptoms increase body weight, or environmental or genetic factors cause both independently. C_LIO_LIPrevious genetic studies have used samples of unrelated individuals to assess the causal impact of BMI on these symptoms, but these studies may have been biased by demographic and familial effects, for example the impact of risk factors correlated with parents BMI. C_LI What this study addsO_LIWhen demographic and family-level effects were controlled for, we found less evidence of an effect of a childs own BMI on depressive, anxiety, or ADHD symptoms, compared with classic MR approaches that do not account for parental genotype. C_LIO_LIWe found evidence that demographic or familial factors correlated with parental BMI may independently impact childrens outcomes. C_LI